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Curated collection of yeast transcription factor DNA binding specificity data reveals novel structural and gene regulatory insights

Raluca Gordân1, Kevin F Murphy1, Rachel P McCord12, Cong Zhu1, Anastasia Vedenko1 and Martha L Bulyk1234*

Author Affiliations

1 Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA

2 Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA

3 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA

4 Harvard-MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, MA 02115, USA

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Genome Biology 2011, 12:R125  doi:10.1186/gb-2011-12-12-r125

Published: 21 December 2011

Abstract

Background

Transcription factors (TFs) play a central role in regulating gene expression by interacting with cis-regulatory DNA elements associated with their target genes. Recent surveys have examined the DNA binding specificities of most Saccharomyces cerevisiae TFs, but a comprehensive evaluation of their data has been lacking.

Results

We analyzed in vitro and in vivo TF-DNA binding data reported in previous large-scale studies to generate a comprehensive, curated resource of DNA binding specificity data for all characterized S. cerevisiae TFs. Our collection comprises DNA binding site motifs and comprehensive in vitro DNA binding specificity data for all possible 8-bp sequences. Investigation of the DNA binding specificities within the basic leucine zipper (bZIP) and VHT1 regulator (VHR) TF families revealed unexpected plasticity in TF-DNA recognition: intriguingly, the VHR TFs, newly characterized by protein binding microarrays in this study, recognize bZIP-like DNA motifs, while the bZIP TF Hac1 recognizes a motif highly similar to the canonical E-box motif of basic helix-loop-helix (bHLH) TFs. We identified several TFs with distinct primary and secondary motifs, which might be associated with different regulatory functions. Finally, integrated analysis of in vivo TF binding data with protein binding microarray data lends further support for indirect DNA binding in vivo by sequence-specific TFs.

Conclusions

The comprehensive data in this curated collection allow for more accurate analyses of regulatory TF-DNA interactions, in-depth structural studies of TF-DNA specificity determinants, and future experimental investigations of the TFs' predicted target genes and regulatory roles.